Translational Value of the Transdermal Administration of Bergamot Essential Oil and of Its Fractions

Scuteri, Damiana; Rombolà, Laura; Crudo, Michele; Watanabe, Chizuko; Mizoguchi, Hirokazu; Sakurada, Shinobu; Hamamura, Keisuke; Sakurada, Tsukasa; Morrone, Luigi Antonio; Tonin, Paolo; Bagetta, Giacinto; Corasaniti, Maria Tiziana

doi:10.3390/pharmaceutics14051006

Cited by 14 publications

(12 citation statements)

References 56 publications

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“…Moreover, it allows us to know the ID50 of NanoBEO which is 0.6312 mg. In fact, the effect of the nanotechnological formulation on 4-methyl histamine-induced scratching behavior increases with the dose, reaching statistical significance at 0.50 and 1 mg. Interestingly, the effect needs at least 30 min to occur, after which it starts to decrease, in agreement with preclinical findings on the different fractions of BEO [ 34 , 35 ]. The single therapeutic dose of NanoBEO confirms its efficacy in the acute phases of nociceptive models in the capsaicin test and the first phase of the formalin test [ 36 ], but also in the sensitization of the formalin test.…”

Section: Discussionsupporting

confidence: 88%

Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia

et al. 2022

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Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics. To this aim, the essential oil of bergamot (BEO), proven by rigorous evidence to have strong preclinical anti-nociceptive and anti-allodynic properties, has been engineered (NanoBEO, patent EP 4003294) to allow randomized, double-blind, placebo-controlled trials (BRAINAID, NCT04321889). The present study: (1) assesses the analgesic effects of a single therapeutic dose of NanoBEO, as supplied by an airless dispenser for clinical translation, in models of inflammatory, neuropathic, and sensitization types of pain relevant to clinic; (2) provides a dose–response analysis of the efficacy of NanoBEO on scratching behavior, a typical behavioral disturbance occurring in dementia. A single therapeutic dose of NanoBEO confirms efficacy following thirty minutes pre-treatment with capsaicin and on the central sensitization phase induced by formalin. Moreover, it has an ID50 of 0.6312 mg and it is efficacious on static and dynamic mechanical allodynia. Altogether, the gathered results strengthen the potential of NanoBEO for clinical management of pain and agitation.

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Section: Discussionsupporting

confidence: 88%

Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia

et al. 2022

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“…Apart from having antinociceptive and antiallodynic properties, BEO is endowed with anxiolytic-like effects devoid of sedative action of benzodiazepines [33], linked to the modulation of serotonergic mechanisms in the animal behavioral tasks Open Field Test, Elevated Plus Maze Test and Forced Swimming Test [34]. Moreover, its fractions are active for inhalation [35] and transdermal [36] application, used in clinic as aromatherapy routes of administration. The analgesic properties of BEO are summarized together with representative studies in Table 2.…”

Section: Results: Essential Oil Of Bergamot As a Paradigm To Followmentioning

confidence: 99%

Pharmacotechnological Advances for Clinical Translation of Essential Oils for the Treatment of Pain and Agitation in Severe Dementia

et al. 2022

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The demand for natural products is steadily increasing, and pharmacotechnological engineering is needed to allow rigorous investigation of their efficacy and safety in clinical conditions representing still unmet needs. Among aged patients affected by dementia, up to 80% of residents in nursing homes suffer from chronic pain and 97% from fluctuant neuropsychiatric symptoms (NPS), of which the most challenging is agitation. It is, at least in part, due to undertreated pain and treated with antipsychotics almost doubling the risk of death. In the frame of a scoping review assessing the existence of essential oils undergoing engineering pharmacotechnological processes using solid lipid nanoparticle delivery systems for clinical translation in pain and/or neuropsychiatric symptoms of dementia following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), here we identified that the sole essential oil engineered to overcome the criticisms of aromatherapy clinical trials in pain and dementia is the essential oil of bergamot (BEO). Therefore, we present the process leading to the actually ongoing randomized, double-blind, placebo-controlled NCT04321889 clinical trial to assess the efficacy and safety of intervention with bergamot in the management of agitation and pain in severe dementia to be followed also for the proof of concept of efficacy and safety of other essential oils.

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“…Moreover, BEO does not have sedative actions [78,79], and this is fundamental for AD patients. Finally, BEO and its fractions can be effectively administered through inhalation and the transdermal route [80,81]. The only reported toxicity of BEO consists of phototoxicity caused by furocoumarins [82].…”

Section: Novel Therapeutic Approaches For Pain and Neuropsychiatric S...mentioning

confidence: 99%

Targeting Neuroplasticity for the Management of Pain and Agitation in Alzheimer’s Disease via Bergamot Nanotherapy

Scuteri¹,

Tonin²,

Corasaniti³

et al. 2022

OBM Neurobiol

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Alzheimer’s disease (AD) accounts for 50–70% of cases of dementia worldwide and is a social burden to the affected population. Although several pathogenetic hypotheses have been proposed, evidence favoring the role of aberrant neuroplasticity in the development of the neuropsychiatric symptoms associated with dementia is increasing. Specifically, agitation is resistant to treatment and affects the quality of life, also because of the lack of safe and effective treatment for AD. Alterations in pain processing due to plastic modifications occur during aging and neurodegeneration. Up to 80% of AD patients have chronic pain due to age-related comorbidities that are misdiagnosed and remain unattended due to a lack of self-reporting because of communication hindrance, which also contributes to the development of agitation. Here, we reported a strategy to target altered neuroplasticity for treating pain and agitation by applying bergamot essential oil with evidence for in-vivo analgesic effects on neuropathic and inflammatory pain preclinical models. Bergamot was engineered in a nanotechnology delivery system, NanoBEO, which provides the opportunity to investigate its efficacy in the NCT04321889 randomized, double-blind, placebo-controlled clinical trial BRAINAID. This trial can provide a rational basis for safe and effective treatment to alleviate agitation and pain, thus improving the quality of life of people suffering from AD.

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Translational Value of the Transdermal Administration of Bergamot Essential Oil and of Its Fractions

Cited by 14 publications

References 56 publications

Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia

Analgesic Characteristics of NanoBEO Released by an Airless Dispenser for the Control of Agitation in Severe Dementia

Pharmacotechnological Advances for Clinical Translation of Essential Oils for the Treatment of Pain and Agitation in Severe Dementia

Targeting Neuroplasticity for the Management of Pain and Agitation in Alzheimer’s Disease via Bergamot Nanotherapy

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